In the late 70ies, it was believed that bacterial diseases were satisfactorily controlled by antibiotics and, as well, future vaccines. Meanwhile, the appearance of new bacterial disease manifestations, such as staphylococcal and streptococcal toxic shock syndrome, the haemolytic-uremic syndrome and others, and rapidly increasing drug resistance worldwide have acted to challenge the view that bacterial diseases were largely defeated.
Antibiotic research at the industrial level was focused on the identification of more refined variants of already existing drugs—and newer penicillins, cephalosporins, macrolides and fluoroquinolones were marketed. However, only one antibiotic based on a novel antimicrobial principle, linezolide, was created during three decades—and resistance to the drug has already emerged during a few years of clinical use. Many antimicrobial peptides with new mechanisms of action have been reported; out of those active against bacteria most target the bacterial cell membrane by forming pores, for example antibiotics which are of microbial origin, and defensins, a large class of substances of mammalian origin. However, so far none of these substances has been developed into clinical use. Also, recent technical progress with combinatorial library technology has enabled the rapid design and testing of many substances intended for a defined target; again, in spite of considerable efforts no such compounds for medical use have been approved to date.Resistance to old and newer antibiotics among bacterial pathogens is evolving rapidly, as exemplified by extended spectrum beta-lactamase (ESBL) and quinolone resistant gram-negatives, multi-resistant gonococci, methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE), penicillin non-susceptible pneumococci (PNSP) and macrolide resistant pneumococci and streptococci (Panlilo et al., Infect Control Hosp Epidemiol 1992;13:582.586; Morris et al., Ann Intern Med 1995;123:250-259). An overuse, or improper use, of antibiotics is probably of great importance for triggering and spread of bacterial resistance.Economically, drug resistant pathogens represent a major burden for health-care systems. For example, postoperative and other nosocomial infections will prolong the need for hospital care and increase antibiotic drug expenses. At the community level, the current situation with PNSP has high-lighted, that most existing antibiotics may fail against this pathogen, earlier known to be invariably susceptible to antibiotics.
In the case of viral diseases, few drugs for treatment are available in spite of intense research. For HIV, the situation has improved by the combined use of some drugs with different targets, delaying progression of the disease. Regarding herpes viruses, there is a need for improved drugs for both systemic and localised manifestations. Also for the SARS virus, effective treatment alternatives are lacking.